提高神经元轴突的生长能力是周围神经再生的关键。周围神经包含感觉神经和运动神经，二者轴突的再生能力存在差异但原因尚不清楚。本项目前期比较了感觉和运动神经元的基因表达谱，发现：1)二者在基因表达的剪接水平差别较大，并可能与轴突生长相关;2)Nova1是二者表达差异最大的RNA结合蛋白，运动神经元高表达，感觉神经元未见表达;3)过表达Nova1的感觉神经元的轴突生长被抑制。因此推测差异表达的Nova1通过调控可变剪接导致了感觉和运动神经元再生能力的差异。在此基础上，拟观察Nova1对感觉和运动神经元轴突生长和再生的作用，通过RNAseq寻找Nova1下游的可变剪接基因，通过构建结构域删除突变体和minigene阐明剪接调控机制，并在动物模型中证实Nova1通路对周围神经再生的作用。本项目将为感觉和运动神经元再生能力差异的原因提供新的理论，也将为提升周围神经再生水平提供新的思路。

Axonal regrowth is critical for peripheral nerve regeneration. Peripheral nerves include sensory and motor nerves, of which the sensory nerves have more robust capacity for regeneration, with unknown mechanisms. By analyzing the gene expression patterns of sensory and motor neurons, we found: 1) splicing levels in these two types of neurons are significantly different, which may be related to axonal growth; 2) Nova1, a RNA binding protein, the most significant differentially expressed gene between these two groups, is highly expressed in motor neurons but not in sensory neurons; 3) Axonal growth is inhibited in sensory neurons with the overexpression of Nova1. Therefore, we infer that the differentially expressed Nova1 accounts for regeneration capacities in sensory and motor nerves by regulating alternative splicing. We will investigate the role of Nova1 in the axonal growth and regrowth of two types of neurons, identify alternative splicing genes downstream of Nova1, and clarify the regulatory mechanisms involved in alternative splicing. Moreover，we will confirm the role of Nova1 pathway in peripheral nerve regeneration in vivo. This project will provide new theories for differential regenerative abilities of sensory and motor neurons, and will offer new ideas for the enhancement of peripheral nerve regeneration.